Phenotypic and genotypic features of -associated cone dystrophy.

PURPOSE

Patients with cone dystrophy (CD) can present with virtually normal retinal appearance, which may delay diagnosis. This study describes the inconspicuous clinical features of -associated CD in two Saudi families.

METHODS

This is a retrospective case study. Clinical data analyzed included multimodal retinal imaging and electroretinography of the affected individuals. Genetic analysis was done for all probands.

RESULTS

Three affected males from two Saudi families with -associated CD were included. The ages at presentation ranged from 18 to 34 years. Ophthalmic examination showed decreased Snellen visual acuities (range: 20/100-20/300) and color vision bilaterally. Fundus examination showed only mild vascular attenuation. Macular optical coherence tomography showed reduced reflectivity of the external limiting membrane, ellipsoid, and interdigitation zones. Full-field electroretinography demonstrated undetectable light-adapted responses and normal dark-adapted responses in all patients. Next-generation sequencing showed one proband to be homozygous for a previously unpublished nonsense variant in (NM_172240):c.672C>G; p(Tyr224*). Whole exome sequencing for the second proband showed a novel homozygous frameshifting variant in : c.991del; p(Arg331Glufs*13).

CONCLUSION

We described two novel variants in and the associated subtle, yet significant retinal features. -associated CD is a rare cause of visual loss in patients with relatively normal fundus appearance. Deep phenotyping is necessary in formulating appropriate differential diagnosis.